Individuals co-infected with HIV and Mycobacterium tuberculosis have an increased risk of developing tuberculosis (TB). Skin testing with purified protein derivative (PPD) is normally used to identify people co-infected with HIV and M. tuberculosis who could benefit from TB chemoprophylaxis; however, the immune deficit induced by HIV may suppress the immune response to PPD, preventing identification of co-infected individuals. A series of skin tests to other common antigens, including mumps and Candida, can be applied to PPD negative, HIV seropositive adults to help determine whether the individuals are anergic or possibly not infected with M. tuberculosis. People who are anergic to PPD, and the battery of other test antigens a?e presumably infected with the TB bacillus but unresponsive to PPD because of, the HIV induced immune deficit. These people might, therefore, benefit from TB chemoprophylaxis; however, the efficacy of chemoprophylaxis in HIV seropositive, PPD negative, anergic adults has not been evaluated thoroughly enough to justify providing it to all such individuals. We propose to conduct an unmasked, randomized clinical trial in Cite Soleil, Haiti to determine the efficacy of two short course TB chemoprophylactic regimens in HIV seropositive, PPD negative, anergic adults with normal chest radiographs. Eligible residents of Cite Soleil (n=345) will be randomized to receive isoniazid and pyridoxine (B6) daily for six months, rifampin and B6 daily for three months followed by daily B6 for three months, or B6 daily for six months. Participants will be followed for 12-54 months and monitored closely for development of active TB, mortality, and progression of HIV infection. Participants with active TB will be treated with the WHO recommended therapeutic regimen. We will determine the efficacy of the chemoprophylactic regimens and evaluate the effect of chemoprophylaxis on survival. We will also evaluate the acceptability and toxicity of the two regimens; identify patient characteristics associated with compliance; identify risk factors for failure of chemoprophylaxis; and determine the prevalence of anergy in HIV seropositive, PPD negative adults with normal chest radiographs in this high risk setting. The results of this study will help establish the efficacy and effectiveness of TB chemoprophylaxis in HIV seropositive, PPD negative, anergic adults in areas where TB is highly endemic.